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Biomedical subjects

M Wettstein

Publications and source records attributed to M Wettstein.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Hepatocellular carcinoma: rising incidence of hepatitis C virus-associated cases at a university clinic in Germany].

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) ranks eighth among malignant tumors worldwide. Western countries belong to areas of low HCC prevalence, but incidence of HCC is rising. The aim of the present, retrospective study was to determine changes in the incidence rates and risk factors for HCC in Germany based on the data of a single center. PATIENTS AND METHODS: Epidemiological data of 205 consecutive patients with HCC (163 males, 42 females, mean age 64+/-1 years), admitted to the University clinic Düsseldorf between January 1988 and December 2001, were evaluated. For comparison this time period was divided into two equal intervals (1988 - 1994 and 1995 - 2001). RESULTS: The number of newly diagnosed HCC has more than doubled in the years 1995 - 2001 compared to the years 1988 - 1994. Chronic hepatitis C (HCV), hepatitis B (HBV), and chronic alcohol abuse accounted for almost 80 % of HCC. The number of HCV-associated HCC increased from 31.0 % in the years 1990 - 1995 to 44.6 % (p < 0.04) in the years 1996 - 2001, whereas the proportion of HBV-associated HCC decreased. There were no changes in the Okuda tumor stage, tumor diameter and alpha-fetoprotein levels at the time of HCC diagnosis throughout the years 1988 - 2001. More than 65 % of HCC were non-resectable at the time of HCC diagnosis due to tumor diameter or number of tumor lesions. CONCLUSION: Screening for HCC, possibly rising in its incidence, should be further improved, taking into account that chronic HCV infection is the major risk factor for HCC in Germany.

Adult↗
PubMed2002

Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy.

The clinical efficacy of both oral and parenteral L-ornithine-L-aspartate (OA) was confirmed by randomized, placebo-controlled, double-blind studies in patients with manifest hepatic encephalopathy and hyperammonemia. The drug was able to reduce high blood ammonia levels induced either by ammonium chloride or protein ingestion or existing as a clinical complication of cirrhosis per se. Furthermore, OA improved performance in Number Connection Test-A as well as mental state gradation. In contrast to the positive effects observed in patients with more advanced hepatic encephalopathy, oral OA does not seem to affect minimal hepatic encephalopathy. In a recent trial, OA decreased protein breakdown and stimulated protein synthesis in muscle. The therapy had little side effects, increasing with higher intravenously administered dosages, and was well tolerated after oral and parenteral administration.

Ammonia↗
PubMed2002

[Clinical outcome of a cohort of 63 patients with hepatocellular carcinoma treated with octreotide].

Unresectable hepatocellular carcinoma (HCC) are associated with a poor prognosis. Recently, one controlled study reported a strikingly prolonged survival of patients with HCC who were treated with octreotide. Until other randomised controlled trials become available, this multicentric retrospective study therefore assesses the outcome of HCC-patients who received octreotide treatment. 63 patients (53 males, 10 females) who had been treated with octreotide at 13 participating German centres were included in the analysis. In 54 cases liver cirrhosis was present (25 Child-Pugh A, 20 Child-Pugh B, 7 Child-Pugh C, 2 unknown). The liver disease was associated with alcohol abuse in 19 patients, alcohol and viral hepatitis in four patients, while 12 patients had only markers of past or present hepatitis B infection, 11 patients suffered of chronic hepatitis C infection, and four patients were seropositive for both hepatitis B and hepatitis C markers. The Okuda stage was stage I in 23, stage II in 33, and stage III in 7 patients. The patients initially received octreotide as a long-acting release formula (20-30 mg/month) in 43 cases or through subcutaneous injection (dose 3 x 50-3 x 300 ug/day) in the remaining cases. 11 of the patients receiving subcutaneous treatment were later converted to the long-acting release form of the drug. At three months, a partial remission was achieved in two patients, while 22 tumours showed no change and 26 tumours progressed. At six months, 11 tumours showed no change, while 15 tumours progressed. The patients' median survival was 9 months (Okuda stage I 16 months, stage II 9 months, stage III 4 months). In conclusion, octreotide treatment did not result in markedly prolonged survival in this retrospective series of 63 patients.

Adult↗
PubMed2001

Modulation of the heme oxygenase HO-1 expression by hyperosmolarity and betaine in primary rat hepatocytes.

The influence of hyperosmotic shrinkage and the osmolyte betaine on heme oxygenase HO-1 expression was studied in cultured rat hepatocytes. Hyperosmolarity transiently suppressed HO-1 induction in response to hemin or medium addition at the levels of mRNA and protein expression. Pretreatment of the cells with betaine largely restored induction of both HO-1 mRNA and protein under hyperosmotic conditions. Exposure of HO-1-expressing hepatocytes to cycloheximide unraveled a hyperosmotic acceleration of HO-1 degradation which was counteracted by betaine and the proteolysis inhibitor MG-132. The HO-1 mRNA stability remained unaffected by hyperosmolarity and betaine as shown by application of the transcription inhibitor actinomycin D. The data suggest a modulation of HO-1 expression by hyperosmolarity and betaine at the transcriptional level and at the level of proteasomal degradation. Hyperosmotic suppression of HO-1 expression was accompanied by a moderate but significant loss of hepatocyte viability, which was prevented by betaine. The hyperosmotic impairment of hepatocyte viability was insensitive to betaine in presence of the heme oxygenase inhibitor zinc protoporphyrin IX. However, treatment of the hepatocytes with bilirubin or 8-Br-cGMP improved hepatocyte viability under hyperosmotic conditions to the control niveau. Thus, stabilizing HO-1 expression may contribute to hepatocyte protection against hyperosmotic stress by organic osmolytes.

Animals↗
PubMed2001

[Nonsurgical therapy methods in hepatocellular carcinoma].

The incidence of the hepatocellular carcinoma (HCC) is increasing in western countries mainly due to chronic hepatitis C. Therapy is dependent on the size and localization of the tumors as well as age and condition of the patient. If resection or transplantation are not possible, smaller tumors can be treated with local therapy either by percutaneous ethanol instillation, radiofrequency ablation or laser thermocoagulation. Larger tumors can be treated by transarterial chemoembolization which can also be combined with the methods named above. The results of systemic chemotherapy and medical treatment are disappointing. With early diagnosis and individualized therapeutic strategies prolongation of life or healing may be reached in many patients.

Carcinoma, Hepatocellular↗
PubMed2001

Regulation of the dynamic localization of the rat Bsep gene-encoded bile salt export pump by anisoosmolarity.

Canalicular transport via the bile salt export pump (Bsep) represents the rate-controlling step in taurocholate excretion, whose capacity is under osmotic control. The short-term effects of anisoosmolarity and Ca(2+)-withdrawal on the localization of Bsep and the tight junction proteins Zo-1 and occludin were studied in perfused rat liver by immunohistochemistry, confocal microscopy, and densitometry. Under normoosmotic conditions, Bsep was found in the canalicular membrane and showed a punctate intracellular localization. Hypoosmolarity resulted in the translocation of intracellular Bsep to the canalicular membrane, whereas hyperosmolarity induced a retrieval of Bsep. Following hyperosmolar retrieval of Bsep and multidrug resistance protein 2 (Mrp2) from the canalicular membrane, in the putative intracellular vesicles Bsep and Mrp2 colocalized in 15% of these vesicles, whereas 85% stained either positive for Bsep (61%) or Mrp2 (24%). Anisotonicity had no effect on the linear staining patterns of occludin and Zo-1, indicating no increase in paracellular permeability. Omission of calcium produced cholestasis characterized by a disruption of occludin, whereas the localization of Zo-1, Bsep, and Mrp2 remained unaffected. It is concluded (1) that hyperosmolarity induces retrieval of Bsep from the canalicular membrane, which correlates to cholestasis. Hypoosmolarity leads to choleresis accompanied by a rapid recruitment of intracellular Bsep to the canalicular membrane. (2) Bsep- and Mrp2-specific vesicles participate in the short-term osmoregulation of canalicular secretion, however, a cause-effect relationship between bile salt excretion and transporter localization remains to be established. (3) Ca(2+)-depletion induces cholestasis by disruption of occludin-determined tight junctional permeability, whereas internalization of canalicular transporters play a minor role.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[Constrictive pericarditis--a differential diagnosis in therapy refractory ascites].

HISTORY AND FINDINGS: A 62-year-old woman with refractory ascites and histologically proven liver cirrhosis was admitted for implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS). Another 44-year-old man presented for evaluation of a liver disease of unknown origin with refractory ascites. DIAGNOSIS, TREATMENT AND COURSE: In both patients abdominal ultrasound showed a dilatation of the inferior caval vein and the liver veins. There was no splenomegaly present. In the side projection of the chest X-ray major calcifications of the pericardium were found pointing to the diagnosis of constrictive pericarditis. Diagnosis was proven by combined left and right heart catheterization demonstrating diastolic dip-plateau-phenomenon. The women was treated successfully by pericardiectomy. CONCLUSIONS: In patients with refractory ascites, dilated jugular veins and dilated liver veins constrictive pericarditis must be suspected. Pericardial calcifications in chest X-ray often given further evidence for the diagnosis which helps to avoid further evaluation of a primary liver disease. The treatment of choice is early surgical pericardiectomy, whereas shunt procedures are not indicated.

Adult↗
PubMed2000

The role of laparoscopic biopsies in lumbar spondylodiscitis.

The infection of an intervertebral disk is a serious condition. The diagnosis often is elusive and difficult to make. It is imperative to have appropriate microbiologic specimens before the initiation of treatment. We report the case of a 51-year-old woman with lumbar spondylodiscitis caused by infection after the placement of an epidural catheter for postoperative analgesia. A spinal magnetic resonance imaging (MRI) scan confirmed the diagnosis, but computed tomography (CT)-guided fine-needle biopsy did not yield adequate material for a microbiologic diagnosis. Laparoscopic biopsies of the involved disk provided good specimens and a diagnosis of Propionibacterium acnes infection. We believe that this minimally invasive procedure should be performed when CT-guided fine-needle biopsy fails to yield a microbiologic diagnosis in spondylodiscitis.

Anesthesia, Epidural↗
PubMed2000

Taurine attenuates cold ischemia-reoxygenation injury in rat liver.

BACKGROUND: Taurine, betaine, and inositol were recently identified as osmolytes in liver cells interfering with cell volume regulation and cell function. In this study, the effect of osmolytes on cold ischemia-reoxygenation injury was investigated in rat liver. METHODS AND RESULTS: Isolated rat livers were flushed for 15 min with Krebs-Henseleit buffer (KHB), then stored for 16 hr in KHB at 4 degrees C, and thereafter reperfused with oxygenated KHB for 180 min. When taurine, betaine, and inositol (2 mmol/L, each) were added to the preperfusion and storage buffer, lactate dehydrogenase, aspartate amino transferase, and glutathione S-transferase leakage into the effluent perfusate during the reoxygenation period were less than half compared to controls without osmolytes and bile flow was higher. The effect of taurine (2 mmol/L) was similar to a mixture of all three osmolytes, indicating that taurine is the most important constituent. When livers were stored for 24 hr in University of Wisconsin solution, osmolyte addition to the storage solution also decreased lactate dehydrogenase and aspartate aminotransferase leakage during reoxygenation. Increasing liver taurine content by a 7-day taurine supplementation of drinking water attenuated reoxygenation injury in cold and warm ischemia in rat livers, whereas taurine depletion by beta-alanine feeding had the opposite effect. CONCLUSIONS: The data show that taurine protects livers from ischemia-reoxygenation. Taurine addition to perfusion and storage solutions in low millimolar concentrations or taurine supplementation of the donor may be useful to protect transplanted organs.

Animals↗
PubMed2000

Electron-microscopic demonstration of multidrug resistance protein 2 (Mrp2) retrieval from the canalicular membrane in response to hyperosmolarity and lipopolysaccharide.

Immunohistochemical studies suggest that canalicular secretion via multidrug resistance protein 2 (Mrp2), a conjugate export pump encoded by the Mrp2 gene, is regulated by rapid transporter retrieval from/insertion into the canalicular membrane. The present study was undertaken in order to investigate this suggestion by means of immunogold electron microscopy. Therefore the effects of lipopolysaccharide (LPS) and osmolarity on Mrp2 localization were studied following immunogold labelling in the perfused rat liver by quantitative electron microscopy and morphometric analyses, and by confocal laser scanning microscopy. Mrp2 activity was assessed in the isolated perfused rat liver by measuring the excretion of dinitrophenyl-S-glutathione as a substrate of Mrp2. Both LPS and hyperosmolarity resulted in a statistically significant decrease in immunogold-labelled Mrp2 in the canalicular membrane and canalicular villi, and an increase in labelling in the pericanalicular cytoplasm. Canalicular morphometric parameters were unchanged under these conditions compared with controls. Under hyperosmolar perfusion Mrp2, but not the canalicular protein dipeptidylpeptidase IV, was found inside the cells, as shown by double immunofluorescence and confocal laser scanning microscopy. The findings suggest a selective retrieval of Mrp2 from the canalicular membrane under the influence of hyperosmolarity and LPS, whereas canalicular morphology remains unchanged.

Animals↗
PubMed2000

Release of osmolytes induced by phagocytosis and hormones in rat liver.

Betaine, taurine, and inositol participate as osmolytes in liver cell volume homeostasis and interfere with cell function. In this study we investigated whether osmolytes are also released from the intact liver independent of osmolarity changes. In the perfused rat liver, phagocytosis of carbon particles led to a four- to fivefold stimulation of taurine efflux into the effluent perfusate above basal release rates. This taurine release was inhibited by 70-80% by the anion exchange inhibitor DIDS or by pretreatment of the rats with gadolinium chloride. Administration of vasopressin, cAMP, extracellular ATP, and glucagon also increased release of betaine and/or taurine, whereas insulin, extracellular UTP, and adenosine were without effect. In isolated liver cells, it was shown that parenchymal cells and sinusoidal endothelial cells, but not Kupffer cells and hepatic stellate cells, release osmolytes upon hormone stimulation. This may be caused by a lack of hormone receptor expression in these cells, because single-cell fluorescence measurements revealed an increase of intracellular calcium concentration in response to vasopressin and glucagon in parenchymal cells and sinusoidal endothelial cells but not in Kupffer cells and hepatic stellate cells. The data show that Kupffer cells release osmolytes during phagocytosis via DIDS-sensitive anion channels. This mechanism may be used to compensate for the increase in cell volume induced by the ingestion of phagocytosable material. The physiological significance of hormone-induced osmolyte release remains to be evaluated.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

[Treatment of coxarthrosis with fitted total hip prostheses replacement].

The treatment of hip osteoarthritis with total hip arthroplasty has continuously evolved since it was first introduced in the sixties. The problem of aseptic loosening of the cemented prostheses, mainly in young active patients, has stimulated two different types of research: on one side the improvement of cementing techniques and on the other side the development of cementless osteoinegrable implants. We discuss the problems of these cementless hip prostheses. Recently published anatomic and biomechanic studies have led to the development of personalized custom femoral stems for each patient. The conception technique and first clinical results are described.

Adult↗
PubMed2000

The role of laparoscopic biopsies in lumbar spondylodiscitis.

Infection of an intervertebral disk is a serious condition. Diagnosis often is elusive and difficult. It is imperative to obtain appropriate microbiological specimens before initiation of treatment. The authors describe a 51-year-old woman with lumbar spondylodiscitis that was because of infection after the placement of an epidural catheter for postoperative analgesia. A spinal magnetic resonance imaging confirmed the diagnosis, but computed tomography-guided fine needle biopsy did not provide adequate material for a microbiologic diagnosis. Laparoscopic biopsies of the involved disk provided good specimens and a diagnosis of Propionibacterium acnes infection. The authors believe that this minimally invasive procedure should be performed when computed tomography-guided fine needle biopsy does not provide a microbiologic diagnosis in spondylodiscitis.

Analgesia, Epidural↗
PubMed1999

[Hepatopulmonary syndrome].

ANAMNESIS: We report about a 60-year-old woman with hepatopulmonary syndrome. The patient suffered from progressive dyspnea and liver cirrhosis following viral hepatitis C, acquired through blood transfusion 30 years ago. EXAMINATION RESULTS: Remarkable were clinical signs of chronic liver disease (cutaneous spider naevi, palmar erythema) and signs of chronic respiratory failure (clubbing) with platypnea. Arterial pO2 was 33 mm Hg under 41 O2/min nasal oxygen supplement and improved to 74 mm Hg under 81 O2/min. Arterial pO2 deteriorated in upright position (orthodeoxia). Contrast enhanced two-dimensional transthoracic echocardiography showed a delayed microbubble opacification in the left heart chambers (without atrial or ventricular septal defect), suggesting pulmonary vascular dilatations. Perfusion scan with macroaggregated albumin labelled with technetium-99m showed uptake over thyroid, kidneys, liver, and spleen suggesting an abnormal passage through the pulmonary vascular bed. The radiological examination with chest radiography and high resolution computer tomography revealed no signs of interstitial lung disease. The pulmonary artery angiography showed neither anatomical shunts nor malformations. DIAGNOSIS: The final diagnosis was hepatopulmonary syndrome Type 1. TREATMENT/FOLLOW-UP: The patient underwent liver transplantation with following good function of the liver graft. After 6 months the patient presented in a much better general condition, but with persisting severe hypoxemia whereas the spider naevi disappeared completely. One year after the liver transplantation in the perfusion scan the uptake over thyroid, kidneys, liver, and spleen was absent. The orthodeoxia and hypoxemia improved evidently. From that we conclude that the pulmonary vascular dilatations diminished after liver transplantation.

Diagnosis, Differential↗
PubMed1999

Regulation of the multidrug resistance protein 2 in the rat liver by lipopolysaccharide and dexamethasone.

BACKGROUND & AIMS: Endotoxin lipopolysaccharide (LPS) induces cholestasis and down-regulates the multidrug resistance protein 2 (MRP2). This study intends to characterize the short-term effects of LPS on MRP2. METHODS: The effects of LPS and dexamethasone on excretion of bromosulphalein (BSP), MRP2 messenger RNA (mRNA) levels, and subcellular MRP2 localization were studied by means of liver perfusion, Northern blots, and confocal microscopy. RESULTS: LPS treatment for 3-12 hours decreased biliary BSP excretion (10 micromol/L) by 40%. Hyposmolarity stimulated BSP excretion to control levels 3 hours after LPS injection, but was ineffective after 12 hours or in saline-treated controls. LPS led to a strong decrease of MRP2 mRNA after 12 hours, but not during the first 6 hours. LPS induced the appearance of MRP2 in intracellular vesicles in the immediate vicinity of the canaliculi within 3 hours, and these vesicles were remote from the canaliculi after 6 and 12 hours. The MRP2-containing vesicles did not stain for dipeptidylpeptidase IV (DPPIV). Dexamethasone counteracted the LPS effects on MRP2 mRNA levels, subcellular distribution, and BSP excretion. CONCLUSIONS: LPS induces cholestasis due to an early retrieval of MRP2 from the canalicular membrane, whereas down-regulation of MRP2 mRNA is a later event. LPS-induced MRP2 retrieval from the canalicular membrane is not associated with the retrieval of DPPIV, suggestive for selectivity of the process.

Animals↗
PubMed1999

Regulation of bile salt export pump mRNA levels by dexamethasone and osmolarity in cultured rat hepatocytes.

The major canalicular bile salt export pump (Bsep) of mammalian liver is downregulated by endotoxin. This study reports on the effects of dexamethasone and osmolarity on Bsep mRNA expression in cultured rat hepatocytes and its functional relevance in rat liver. Expression of Bsep mRNA in rat hepatocytes 24 and 48 h after isolation was dependent on the presence of dexamethasone (100 nM) in the culture medium. Bsep was functionally active at the pseudocanalicular membrane in cells cultured for 4 days in medium containing dexamethasone. Hypoosmolarity (205 mosmol/l) led to an induction of Bsep mRNA levels, whereas expression was decreased by hyperosmolarity (405 mosmol/l). Also the decay of Bsep mRNA following dexamethasone withdrawal was osmosensitive. In rat liver, dexamethasone counteracted the lipopolysaccharide (LPS)-induced down-regulation of Bsep mRNA levels after 12 hours and abolished the LPS-induced inhibition of taurocholate excretion. These results indicate that glucocorticoids are strong inducers of Bsep in liver. Furthermore, Bsep mRNA levels are osmosensitively regulated. The data suggest a longterm control of Bsep mRNA by osmolarity in addition to the short-term effects on canalicular bile acid excretion, which were reported recently.

ATP Binding Cassette Transporter, Subfamily B, Mem↗